Interaction of the DRD3 and BDNF gene variants in subtyped bipolar disorder
Journal
Progress in Neuro-Psychopharmacology and Biological Psychiatry
Journal Volume
39
Journal Issue
2
Pages
382-387
Date Issued
2012
Author(s)
Lee S.-Y.
Chen S.-L.
Chen S.-H.
Chu C.-H.
Chang Y.-H.
Lin S.-H.
Huang S.-Y.
Tzeng N.-S.
Lee I.H.
Yeh T.L.
Yang Y.K.
Abstract
Objectives: Bipolar disorder is a severe mental disorder with prominent genetic etiologic factors. Dopaminergic dysfunction has been implicated in the pathogenesis of bipolar disorder, which suggests that the dopamine D3 receptor gene (DRD3) is a strong candidate gene. The brain-derived neurotrophic factor (BDNF) gene has been implicated in the etiology of bipolar disorder. We examined the association between the BDNF Val66Met and DRD3 Ser9Gly polymorphisms with two subtypes of bipolar disorder: bipolar-I and -II. Because BDNF regulates DRD3 expression (1), we also examined possible interactions between these genes. Methods: We recruited 964 participants: 268 with bipolar-I, 436 with bipolar-II, and 260 healthy controls. The genotypes of the BDNF Val66Met and DRD3 Ser9Gly polymorphisms were determined using polymerase chain reactions plus restriction fragment length polymorphism analysis. Results: Logistic regression analysis showed a significant main effect for the Val/Val genotype of the BDNF Val66Met polymorphism (P = 0.020), which predicted bipolar-II patients. Significant interaction effects for the BDNF Val66Met Val/Val genotype and both DRD3 Ser9Gly Ser/Ser and Ser/Gly genotypes were found only in bipolar-II patients (P = 0.027 and 0.006, respectively). Conclusion: We provide initial evidence that the BDNF Val66Met and DRD3 Ser9Gly genotypes interact only in bipolar-II disorder and that bipolar-I and bipolar-II may be genetically distinct. ? 2012 Elsevier Inc.
SDGs
Other Subjects
brain derived neurotrophic factor; dopamine 3 receptor; amino acid substitution; article; bipolar I disorder; bipolar II disorder; brain derived neurotrophic factor gene; controlled study; disease classification; dopamine 3 receptor gene; gene expression regulation; gene function; gene interaction; genetic association; genetic polymorphism; genetic variability; human; human cell; major clinical study; molecular pathology; polymerase chain reaction; restriction fragment length polymorphism; Adult; Bipolar Disorder; Brain-Derived Neurotrophic Factor; Case-Control Studies; Female; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Male; Polymorphism, Single Nucleotide; Receptors, Dopamine D3
Type
journal article